Process for preparing diosmin and flavonoid fraction

Abstract

Process for the preparation of diosmin and flavonoid fraction by direct oxidation of hesperidin.

1 - 12 . (canceled) 
     
     
         13 . A process for the preparation of diosmin by oxidation of hesperidin via an iodine-donating oxidizing couple, at a temperature of 80 to 120° C., in a mixture of polar aprotic solvent and acetic acid, followed by isolation by added water, filtration, rinsing and drying. 
     
     
         14 . The process according to  claim 13 , wherein the diosmin obtained is in the form of Pharmacopoeia Diosmin, comprising from 90.0 to 102.0% diosmin, less than 4.0% hesperidin, less than 2.0% diosmetin, less than 3.0% isorhoifolin, less than 3.0% linarin and less than 0.6% 6-iododiosmin. 
     
     
         15 . The process according to  claim 13 , wherein the diosmin obtained is in the form of a flavonoid fraction comprising from 86.0 to 95.0% diosmin, from 2.5 to 6.0% hesperidin, from 0.2 to 2% diosmetin, from 0.8 to 3.5% linarin and from 0.8 to 3.5% isorhoifolin. 
     
     
         16 . The process according to  claim 13 , wherein the diosmin obtained contains less than 0.6% 6-iododiosmin. 
     
     
         17 . The process according to  claim 15 , wherein diosmin obtained contains less than 0.6% 6-iododiosmin. 
     
     
         18 . The process according to  claim 13 , wherein the iodine-donating oxidizing couple is selected from NaI/H 2 O 2 , KI/H 2 O 2 , TBAI/H 2 O 2  and NaI/I 2 /H 2 O 2 . 
     
     
         19 . The process according to  claim 18 , wherein the iodine-donating oxidizing couple is NaI/H 2 O 2 . 
     
     
         20 . The process according to  claim 19 , wherein the amount of NaI is from 0.4 to 0.8 molar equivalent with respect to the hesperidin employed. 
     
     
         21 . The process according to  claim 18 , wherein the amount of hydrogen peroxide is from 0.9 to 1.1 molar equivalents relative to the hesperidin employed. 
     
     
         22 . The process according to  claim 13 , wherein the polar aprotic solvent is dimethyl sulfoxide. 
     
     
         23 . The process according to  claim 13 , wherein the diosmin obtained is purified by a base/acid treatment. 
     
     
         24 . The process according to  claim 13 , wherein the crude diosmin obtained is first reslurried in an organic solvent, including dimethyl sulfoxide, N-butylpyrrolidone, pyridine, sulfolane, dimethyl carbonate and propylene carbonate, or in a mixture of organic solvent and water, including a mixture of pyridine and water, then filtered and rinsed with water, before undergoing a base/acid treatment. 
     
     
         25 . The process according to  claim 13 , wherein the diosmin obtained is purified by a base/acid treatment in the presence of hydrogen peroxide.